MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome.

ABSTRACT: The neurodevelopmental disorder Pitt Hopkins syndrome (PTHS) causes clinical symptoms similar to Rett syndrome (RTT) patients. However, RTT is caused by MECP2 mutations whereas mutations in the TCF4 gene lead to PTHS. The mechanistic commonalities underling these two disorders are unknown, but their shared symptomology suggest that convergent pathway-level disruption likely exists. We reprogrammed patient skin derived fibroblasts into induced neuronal progenitor cells. Interestingly, we discovered that MeCP2 levels were decreased in PTHS patient iNPCs relative to healthy controls and that both iNPCs and iAstrocytes displayed defects in function and differentiation in a mutation-specific manner. When Tcf4^+/- mice were genetically crossed with mice overexpressing MeCP2, molecular

SUBMITTER: Dennys CN 

PROVIDER: S-EPMC11579869 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature